ABSTRACT
Tumor necrosis factor (TNF) plays a pivotal role in the early control of Mycobacterium tuberculosis and M. avium infections by a host. It was previously shown that both phagocyte-derived and T-cell-derived TNF productions are critical for protective immunity against M. tuberculosis, but the role of TNF produced by B-cells remained unclear. By comparing mice with B-cell-specific TNF deletion to littermate control mice, here we show that TNF production by B-lymphocytes is essential for the formation of infection-specific aggregates of B-cells in the lung. It is likely that these compact foci represent a pathogenic feature of inflammatory response rather than an element of protective immunity, since the capacity to form aggregates has no influence on the severity of M. tuberculosis- and M. avium-triggered diseases.
Subject(s)
B-Lymphocytes/cytology , B-Lymphocytes/metabolism , Lung/immunology , Lung/microbiology , Mycobacterium avium/immunology , Mycobacterium tuberculosis/immunology , Tumor Necrosis Factor-alpha/biosynthesis , Animals , B-Lymphocytes/immunology , Cell Aggregation , Mice , Mice, Inbred C57BL , Tumor Necrosis Factor-alpha/deficiency , Tumor Necrosis Factor-alpha/immunologyABSTRACT
A proof of concept study has been conducted for the design of a porous biodegradable material containing nanocapsules and two actives with independent release-bimodal drug-eluting implants. Completely safe synthetic material free from risk of prion and virus contamination was tested in vivo, and a method for controlling the rate of biodegradation of poly-2-cyanoacrylic polymer was developed. Novel perfluorinated 2-cyanoacrylic esters have been applied for the chemical modification of polyethyl-2-cyanoacrlylate copolymers. Internal imide-cycle formation has been used to retard the rate of enzymatic hydrolysis of the 2-cyanoacrylic copolymer main chain.